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Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis.

ABSTRACT: BACKGROUND:Endoscopic and histologic healing are emerging as new therapeutic goals in ulcerative colitis (UC), as these endpoints are associated with less relapse, hospitalization and colectomy. AIM:To investigate the association of serum infliximab trough concentrations during maintenance therapy with endoscopic or histologic healing in UC. METHODS:In this multi-center retrospective cohort study, we included consecutive patients with moderate-to-severe UC on infliximab maintenance therapy who had an endoscopic evaluation and underwent therapeutic drug monitoring within three months of the colonoscopy, between February 2008 and March 2016. Per event analysis was performed. Endoscopic healing was defined as Mayo endoscopic sub-score of ?1. Histologic healing was defined as no or only focal mild active inflammation. RESULTS:Seventy colonoscopies from 56 patients were evaluated. Infliximab trough concentrations (median [interquartile range]) were significantly higher in patients with endoscopic (11.3 [7.6-14.5] vs 6.3 [0-9.8] ?g/mL, P < .001) or histologic (11.1 [6.7-14.5] vs 6.7 [0-9.9] ?g/mL, P = .002) healing, respectively, compared to patients without healing. Receiver-operating characteristic analyses identified infliximab trough concentration thresholds of 7.5 (area under the curve [AUC]: 0.758) and 10.5 (AUC: 0.721) ?g/mL to be associated with endoscopic and histologic healing, respectively. Multiple logistic regression analysis identified infliximab trough concentration ?7.5 (P = .013; odds ratio [OR]: 4.3; 95% confidence intervals [CI]: 1.4-13.3) and ?10.5 ?g/mL (P = .013; OR: 3.8; 95% CI: 1.3-11) as independent factors associated with endoscopic and histologic healing, respectively. CONCLUSIONS:This study demonstrated that infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in patients with UC.

SUBMITTER: Papamichael K

PROVIDER: S-EPMC6535226 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis.

Papamichael K K Rakowsky S S Rivera C C Cheifetz A S AS Osterman M T MT

Alimentary pharmacology & therapeutics 20171206 4

<h4>Background</h4>Endoscopic and histologic healing are emerging as new therapeutic goals in ulcerative colitis (UC), as these endpoints are associated with less relapse, hospitalization and colectomy.<h4>Aim</h4>To investigate the association of serum infliximab trough concentrations during maintenance therapy with endoscopic or histologic healing in UC.<h4>Methods</h4>In this multi-center retrospective cohort study, we included consecutive patients with moderate-to-severe UC on infliximab mai ...[more]

PMID: 29210094

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Project description:BACKGROUND AND AIMS:Recent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes. METHODS:In this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ?35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired. RESULTS:A total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p?=?0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission (p?=?0.04, p?<?0.001, and p?=?0.01, respectively). In a multivariate analysis, a PUCAI ?65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure (p?=?0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p?=?0.05). Kaplan-Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1-15.6%) in children with severe UC and 3.92% (95% CI 2.9-10.8%) in patients with moderate UC (logrank test p?=?0.06). CONCLUSIONS:Children starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.

Project description:BackgroundEndoscopic and histological activity scores in ulcerative colitis (UC) are associated with clinical outcomes and have become important targets of clinical trials. However, these endpoints have been scarcely investigated in patients receiving only conventional treatment.ObjectiveWe aimed to assess the deep and complete remission rates after 3 months of conventional treatment in patients with newly diagnosed UC with moderate to severe endoscopic activity. We also aimed to investigate whether selected clinical and biochemical variables at baseline were associated with complete remission status after 3 months.DesignThis was a prospective cohort study.MethodsNewly diagnosed patients with active UC commencing 5-aminosalicylate, corticosteroid, and/or azathioprine treatment were consecutively included. Clinical, biochemical, endoscopic, and histological data were collected at baseline and after 3 months. Rates of clinical remission (Partial Mayo Score ⩽ 2), mucosal healing (Mayo Endoscopic Score ⩽ 1), and histologic healing (Nancy Index ⩽ 1) were determined. Deep remission was assessed as clinical remission plus mucosal healing and complete remission as deep remission plus histologic healing. Predictors of complete remission were identified by logistic regression.ResultsA total of 180 patients were included in the study. Deep remission and complete remission occurred in 62.8% and 42.2% of patients, respectively. Thus, of patients in deep remission one-third had persistent histologic activity. Histologic activity in mucosally healed patients was associated with higher symptom scores and faecal calprotectin levels. Of baseline variables, less endoscopic distribution and disease activity showed strongest association with achieving complete remission, and limited distribution in combination with moderate activity gave highest odds for complete remission (odds ratio: 4.1, 95% confidence interval: 7.69-2.18).ConclusionIn patients with mucosal healing, persistent histologic activity was a common finding and was associated with increased disease activity. Pancolitis and severe inflammatory activity at baseline were associated with lower complete remission rates.

Project description:BackgroundAchieving endoscopic remission is a key therapeutic goal in patients with ulcerative colitis (UC) that is associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of endoscopic and/or histologic remission against ileal barrier healing for predicting long-term disease behavior in a large cohort of UC patients in clinical remission.MethodsAt baseline, UC patients in clinical remission underwent ileocolonoscopy with assessment of ileal barrier function by confocal endomicroscopy. Endoscopic and histologic disease activity and ileal barrier healing were scored using validated scores. During subsequent follow-up (FU), patients were closely monitored for clinical disease activity and occurrence of major adverse outcomes (MAO) defined as the following: disease relapse; UC-related hospitalization; UC-related surgery; necessity for initiation or dose escalation of systemic steroids, immunosuppressants, small molecules or biological therapy.ResultsOf the 73 UC patients included, 67% experienced MAO during a mean FU of 25 months. The probability of MAO-free survival was significantly higher in UC patients with endoscopic and/or histologic remission compared to patients with endoscopically and/or histologically active disease. Ileal barrier healing on endomicroscopy was highly accurate for predicting the further course of UC and outcompeted endoscopic and histologic remission for predicting MAO-free survival.ConclusionIleal barrier healing in clinically remittent UC patients can accurately predict future MAO development and is superior in its predictive capabilities than endoscopic and histologic remission. Ileal barrier healing therefore represents a novel and superior surrogate parameter for stratification of UC patients according to their risk for development of complicated disease behavior.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05157750, identifier NCT05157750.

Dataset Information

Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis.

Publications

Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis.

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